Droplet microfluidics for bioprocess Engineering

Abstract

A crucial challenge during the initial stages of bioprocess development is that tools used to screen microorganisms and optimize cultivation conditions do not represent the environment imposed at industrial scale. Inside an industrial-scale bioreactor, microorganisms are often cultivated under fed-batch conditions, where nutrients are supplied during the culture. Additionally, microorganisms continuously keep crossing zones with low and high concentrations of substrate and dissolved oxygen. However, during initial bioprocess development, growth and productivity of microorganisms are evaluated under batch conditions due to the difficulty of dynamically controlling nutrient and dissolved oxygen concentrations in screening equipment such as micotiter plates. This inconsistency in cultivation conditions often leads to selection of strains that fail to perform at industrial scale. The difficulty in continuously supplying minute amounts of nutrients to microorganisms in microtiter plates and imposing dynamic dissolved oxygen levels throughout the cultivation experiment necessitates an alternative approach. Microfluidic technology holds the potential to address this inconsistency with fidelity by offering high-throughput experimentation and excellent control over the culture microenvironment. The central theme of this Ph.D. project is the design and development of droplet-based microfluidic technology, that enable studying microorganisms under such dynamically controlled cultivation conditions. As such, the outcomes from this Ph.D. project form a foundation step towards narrowing the gap between screening and industrial-scale use, with an eye to keeping the technology sufficiently simple to be adopted by the biotechnology and bioengineering community. We start by reviewing different types of scalable micro-bioreactor